Effect of carbon tetrachloride-induced liver damage on organic ion transport in rat liver

Abstract

The effect of carbon tetrachloride (CCl 4) pretretment on the hepatic transport of a cation, procaine amide ethobromide (PAEB), and of an anion, p-acetylaminohippurate (PAAH), was investigated in anesthetized rats with ligated renal pedicles and a cannulated bile duct. Each animal received a single ip injection of CCl 4 (1 ml/kg) as a 50% solution in olive oil at times ranging from 0.5 to 71.5 hr prior to an iv injection of PAEB, 5 mg/kg, or PAAH, 20 mg/kg. Control animals were pretreated with olive oil alone. The effect of CCl 4 on the biliary excretion rate of PAEB and on the concentration of PAEB in liver 30 min after injection of the cation varied with the time after CCl 4 pretreatment. At 1, 2, 4 and 7 hr after CCl 4 treatment, the biliary excretion rate of PAEB was depressed, while the concentration of the drug in liver was markedly elevated. The results suggested that the main effect of CCl 4 was to decrease the transport of PAEB from liver to bile. In the case of PAAH, there was an increase in the plasma concentration, a decrease in liver concentration, and an even greater decrease in the biliary excretion rate of the compound at all times between 0.5 and 48 hr after CCl 4 treatment. The results suggested that the effect of CCl 4 treatment was to depress the net transport of PAAH from plasma to liver and also from liver to bile.